Dialkyltin salts of substituted pyridine-1-oxides as fungicides and bactericides

ABSTRACT

CERTAIN DIALKYLTIN SALTS OF 2-MERCAPTOOPYRIDINE-1-OXIDE AND 2-HDROXYPYRIDINE-1-OXIDE ARE PREPARED BY REACTING THE RESPECTIVE OXIDES WITH A DIALKYLTIN SLAT OF A LOW MOLECULAR WEIGHT ORGANIC OR INORGANIC ACID. THE RESULTING SALTS ARE HIGHLY EFFECTIVE BACTERICIDES AND FUNGICIDES WHICH HAVE ESPECIALLY LOW TOXICITY TO HIGHER ANIMALS.

3,705,943 DIALKYLTIN SALTS OF SUBSTITUTED PYRIDINE- 1-OXIDES ASFUNGICIDES AND BACTERICIDES Charles W. Kaufman, Hamden, Cnn., assignorto Olin Corporation, New Haven, Conn.

No Drawing. Continuation-impart of application Ser. No. 596,801, Nov.25, 1966. This application July 18, 1969, Ser. No. 843,218

Int. Cl. A01n 9/22 US. Cl. 424-245 7 Claims ABSTRACT OF THE DISCLOSURECertain dialkyltin salts of Z-mercaptopyridine-l-oxide and2-hydroxypyridine-l-oxide are prepared by reacting the respective oxideswith a dialkyltin salt of a low molecular weight organic or inorganicacid. The resulting salts are highly effective bactericides andfungicides which have especially low toxicity to higher animals.

wherein R and R" are independently selected from the group consisting ofalkyl of from 4 to 8 carbon atoms and Ch is a chalcogen selected fromthe group consisting of sulfur and oxygen.

The compound herein referred to as Z-mercaptopyridinel-oxide, althoughgenerally represented as:

is believed to be a mixture of two tautomeric isomers as follows:

SH Ti [is N N l 0 OH In a like manner the compound herein referred to as2-hydroxypyridine-l-oxide, although generally represented as:

United States Patent 0 ice is believed to be a mixture of two tautomericisomers as This tautomerism will not be alluded to hereinafter, it beingunderstood that the tautomeric forms of I and II are included whenreferring to the compounds of this invention either by formulae such asI and II or by name.

The compounds of this invention can be prepared by a method whichcomprises interacting Z-mercaptopyridinel-oxide or2-hydroxypyridine-l-oxide, preferably in the form of a soluble salt,such as an alkali metal salt or ammonium salt thereof, with a dialkyltinsalt of a lower molecular weight organic or inorganic acid in a solventfor the reactants and recovering the reaction product.

Dialkyltin salts suitable for use as starting materials of the processof this invention have the formula:

wherein R and R" are independently selected from the group consisting ofalkyl of from 4 to 8 carbon atoms and X is the anion of a lowermolecular weight inorganic or organic acid. The anions which may bementioned include nitrates, acetates, formates, sulfates and halides.Suitable anions have an atomic or molecular weight below about 127.

Preferably, the reaction is carried out using substantiallystoichiometric proportions of the two reactants. The reaction can beconducted in a wide variety of inert organic solvents.- Monohydricalcohols, such as methanol, ethanol, butanol, etc. and hydrocarbonsolvents such as benzene, toluene or xylene, are particularly usefulsolvents. The product can be recovered from the reaction mixture by anyof a number of methods well known in the art, such as by filtration toremove insoluble products formed during the reaction following which thedesired product can be recovered from the filtrate by evaporation,extraction with solvents or by any other convenient methods.

Useful dialkyltin salts include, for example:

di-n-butyltin dichloride, sec.-butyl n-octyl dichloride, isoamyln-hexyltin dibromide, di-n-octyltin dichloride, di-n-octyltin dibromide,di-n-octyltin sulfate, di-n-octyltin dinitrate, di-n-octyltin diacetate,di-isooctyltin diformate, di-isooctyltin diiodide, and di-n-heptyldichloride.

The following examples are illustrative of, but not limitative of, theinvention.

EXAMPLE I Di-n-butyltin salt of Z-mercaptopyridine-l-0xide Di-n-butyltindichloride was dissolved in 50 ml. of methanol. A solution of 0.10 moleof the sodium salt of Z-mercaptopyridine-l-oxide in 150 ml. of methanolwas added to the di-n-butyltin dichloride solution with stirring. Thenthe mixture was heated on steam bath for 0.5 hour and filtered hot. Thefiltrate was chilled to 10 C. and 0.035 mole of white crystals, M.P. 92C., was recovered representing a 70 percent yield of the di-n-butyltinsalt of 2-mercaptopyridine-l-oxide having the formula:

Analysis-Cam. for C H N O S Sn (percent): C, 44.4; H, 5.34; N, 5.76; Sn,24.3. Found (percent): C, 44.35, 44.32; H, 5.36, 5.45; N, 5.80, 5.91;Sn, 22.7.

EXAMPLE II Di-n-octyltin salt of Z-mercaptopyridinel-oxide A solution of0.1 mole of the sodium salt of 2-mercap topyridine-l-oxide in 100 ml. ofmethanol was added to 0.05 mole of di-n-octyltin dichloride in 100 ml.methanol. A white precipitate formed which was filtered oil. The filtercake was recrystallized from acetone giving 41 percent yield of thedioctyltin salt of Z-mercaptopyridinel-oxide, M.P. 9093 C. having theformula:

EXAMPLE III Di-n-butyltin salt of 2-hydroxypyridine-l-oxide ing theformula:

ll-C411 /Sn-O N/ 11- 4 0 L i EXAMPLE IV Di-n-octyltin salt ofZ-hydroxypyridine-l-oxide To di-n-octyltin dichloride, 20 g. (0.05 mole)dissolved in 150 ml. of methanol, there was added 22 g. (0.10 mole) of2-hydroxypyridine-l-oxide with stirring. Then 6.5 g. of sodium hydroxidedissolved in 100 ml. of methanol was added following which the reactionmixture was boiled for 20 minutes and filtered hot. After the filtratehad been concentrated on a steam bath to 115 ml. it was chilled to atemperature of about 10 C. The white solid which precipitated wasrecovered and then recrystallized from methanol. A total of 12.0 g. ofthe di-n-octyltin salt of 2-hydroxypyridine-l-oxide, M.-P. 6870 C. (41percent yield of the theoretical yield) having the formula:

/Sn -CH n s n L 5 2 was obtained.

was obtained.

TABLE I.ANTIBACTERIAL SPECTRUM M.I.C. ig/ml.

Organism A B C D Staphylococcus aureus P209 0.08 0.10 0. 37 0. 06Bacillus sublz'lis 0. 047 0. 19 18. 7 Strepto coccasfaecalzs. 0. 0. 419. 4 Klebsiella pneumoniae- 4. 7 4. 8 100. 0 1S. 7 Pscudomonas aemginosal8. 7 25. 0 75.0 6. 3 Proteus vulgaris l8. 7 1B. 7 100. 0 Escherichiacoli 9.4 14.0 100. 0 Salmonella scholtmuellerz 9. 4 8. 6 100. 0Aerobacter aerogenes 6. 3 4. 7 75. 0 Mgcobacterium tuberculosis BOG 0.04 4. 7 0. 32 Desulfovibrio desulfricans 0.13

N0'rn.-A=Di-n-butyltin salt or Z-mereaptopyridine-l-oxide.B=Din-oetyittn salt of Q-mercaptopyIidine-l-oxide. C=Di-n-octyltln salt01 2-hydroxypyridinel-oxide. D =Hexaehlorophene.

TABLE IL-ANIIFUN GAL SPECTRUM Trichophyton mentagrophyt 0. 39 0. 28Aapergillus fumigatus 0. 39 0. 63 Aspergillus 'mger 0. 25 1. 8Pullu-laria pullullans 0. 08 0. 72

1 Names of the individual compounds are given in footnotes of Table I.

Although the zinc salt of Z-mercaptopyridine-l-oxide is a highlyefiective antibacterial agent for many applications, its extremely lowsolubility in materials, such as organic solvents, prevents its use incertain important applications. In contrast, the compounds of thisinvention which have appreciable solubility in, for example, methylalcohol, ethyl alcohol, acetone, hexane, xylene, can be convenientlyintroduced into a product or process as a solution of the compound inthe solvent. In Table III which follows the solubility of some of thecompounds of this invention in various solvents is shown (data on thezinc salt of Z-mercaptopyridine-l-oxide being included for comparison):

1 Insoluble.

Certain other organic tin salts of Z-hydroxypyridine-ioxide haveantibacterial and/ or antifungal properties but are not suitable for manuses due to their high toxicity to higher animals. Table IV presentsdata on the LD dose of some of the compounds of this invention comparedwith other compounds showing the markedly low toxicity of the productsof this invention against mice.

TABLE IV Compound: Acute oral LD Di-n-butyltin salt ofZ-mercaptopyridine-l- Di-n-octyltin salt of Z-hydroxypyridine-loxide(product of Example IV) 2000 Since the compounds of this inventionpossess broad antibacterial and antifungal properties, they are utilizedas preservatives in a wide variety of products, as mildew proofingagents, and for sterilization and disinfecting purposes. The compoundsof this invention are especially useful as preservatives in leather,paint, paper, etc. and in plastics and other fabrics to render themproof against mildew or other fungus attack. In the protection offabrics, for example, with a compound of this invention, the compoundmay be applied or incorporated in the fabric in a number of ways such asby soaking or spraying it with hexane solution of the compound, forexample, ethyl alcohol, hexane, or xylene and then allowing the solventto evaporate. Suitably an effective amount of a compound of theinvention is applied to the substrate, for example, from about 0.001 to1 percent by weight.

What is claimed is:

1. A method for controlling the growth of fungi and bacteria on a locuswhich comprises applying to the locus to be protected an efiectivefungicidal or bactericidal amount of a compound having the formula:

the formula I1- 0 $1; I l

Sn- S n-CsHn 6. The method of claim 1 wherein said compound has theformula:

n- C 4H9 Sn-O 7. The method of claim 1 wherein said compound has theformula:

was

/Sn0 N/ n-OaHn l References Cited UNITED STATES PATENTS 2,809,97110/1957 Bernstein et al. 424-245 ALBERT T. MEYERS, Primary Examiner V.D. TURNER, Assistant Examiner US. Cl. X.R. 260-270 R

